Hypoglycaemia Medical Assignment Help

Hypoglycaemia develops when hepatic glucose output falls below the rate of glucose uptake by peripheral tissues. Hepatic glucose output may be reduced by:
• The inhibition of hepatic glycogenolysis and gluconeogenesis by insulin
• Depletion of hepatic glycogen reserves by malnutrition, fasting, exercise or advanced liver disease
• Impaired gluconeogenesis (e.g. following alcohol ingestion)
In the first of these categories, insulin levels are raised, the liver contains adequate glycogen stores, and the hypoglycaemia can be reversed by injection of glucagon. In the other two situations, insulin levels are low and glucagon is ineffective.
Peripheral glucose uptake is accelerated by high insulin levels and by exercise, but these conditions are normally balanced by increased glucose output. Insulin or sulphonylurea therapy for diabetes accounts for the vast majority of cases of severe hypoglycaemia encountered in an accident and emergency department.
The commonest symptoms and signs of hypoglycaemia are neurological. The brain consumes about 50% of the total glucose produced by the liver. This high energy requirement is needed to generate ATP used to maintain the potential difference across axonal membranes.

Insulinomas

Insulinomas are pancreatic islet cell tumours that secreteinsulin. Most are sporadic but some patients have multiple tumours arising from neural crest tissue (multiple endocrine neoplasia). Some 95% of these tumours are benign. The classic presentation is with fasting hypoglycaemia, but early symptoms may also develop in the late morning or afternoon. Recurrent hypoglycaemia is often present for months or years before the diagnosis is made,
and the symptoms may be atypical or even bizarre; the presenting features in one series are given. Common misdiagnoses include psychiatric disorders, particularly pseudo dementia in elderly people, epilepsy and cerebrovascular disease.

DIAGNOSIS

Whipple’s triad remains the basis of clinical diagnosis. This is satisfied when:
1 Symptoms are associated with fasting or exercise
2 Hypoglycaemia is confirmed during these episodes
3 Glucose relieves the symptoms
A fourth criterion – demonstration of inappropriately high insulin levels during hypoglycaemia-may usefully be added to these.
In practice, the diagnosis is confirmed by the demonstration of hypoglycaemia in association with inappropriate and excessive insulin secretion. Hypoglycaemia is demonstrated by:
MEASUREMENT OF OVERNIGHT FASTING (16 HOURS) GLUCOSE AND INSULIN LEVELS ON THREE OCCASIONS. About 90% of patients with insulinomas will have low glucose and non-suppressed (normal or elevated) insulin levels.
PERFORMING A PROLONGED 72 HOUR SUPERVISED FAST if overnight testing is inconclusive and symptoms persist.
Autonomous insulin secretion is demonstrated by lack of the normal feedback suppression during hypoglycaemia. This may be shown by measuring insulin, C-peptide or proinsulin during a spontaneous episode of hypoglycaemia. Many patients also have an abnormal (diabetic) glucose tolerance test, but this has no diagnostic value.

The most effective therapy is surgical excrsion of the tumour. Insulinomas are often very small and difficult to localize. Highly selective angiography and contrastenhanced CT scanning are used in the first instance. Highly selective angiography is very operator dependent and referral to a skilled operator is warranted if initial attempts at localization fail. ‘Blind’ laparotomy runs the risk that the surgeon may be unable to find the insulinoma and resorts to partial pancreatectomy, with unpleasant consequences if the tumour remains in the unexcised pancreas. Localization is also possible using a rapid insulin assay on blood sampled at different levels from the pancreatic vein.
Medical treatment with diazoxide is useful when the insulinoma is malignant, in patients in whom a tumour cannot be located, and in elderly patients with mild symptoms. Symptoms may remit on treatment with the somatostatin analogue octreotide.

Hypoglycaemia with other tumours

Hypoglycaemia may develop in the course of advanced neoplasia and cachexia, and has been described in association with many tumour types. Certain massive turnours, especially sarcomas, may produce hypoglycaemia due to secretion of insulin-like growth factor 1. True ectopic insulin secretion is extremely rare.

Postprandial hypoglycaemia

If frequent venous blood glucose samples are taken following a prolonged glucose tolerance test, about one in four subjects will have at least one value below 3 mmollitre-1
• The arteriovenous glucose difference is quite marked during this phase, so that very few are truly hypoglycaemic in terms of arterial (or capillary) blood glucose content. Failure to appreciate this simple fact led some authorities to believe that postprandial (or reactive) hypoglycaernia was a potential ‘organic’ explanation for a variety of complaints that might otherwise have been considered psychosomatic. An epidemic of false ‘hypoglycaernia’ followed, particularly in the USA. Later work showed a poor correlation between symptoms and biochemical hypoglycaemia. Even so, a number of otherwise normal people occasionally become pale, weak and sweaty at times when meals are due, and report benefit from advice to take regular snacks between meals. True postprandial hypoglycaemia may develop in the presence of alcohol, which ‘primes’ the {3cells to produce an exaggerated insulin response to carbohydrate. The person who substitutes alcoholic beverages for lunch is particularly at risk. Postprandial hypoglycaemia sometimes
occurs after gastric surgery, owing to rapid gastric emptying and mismatching of food and insulin. This is referred to as ‘dumping’ but it is now rarely encountered.
Hepatic and renal causes of hypog Iycaemia The liver can maintain a normal glucose output despite extensive damage, and hepatic hypoglycaemia is uncommon. It is particularly a problem with fulminant hepatic failure.
The kidney has a subsidiary role in glucose production (via gluconeogenesis in the renal cortex), and hypoglycaemia is sometimes a problem in terminal renal failure. Hereditary fructose intolerance occurs in 1 in 20000 live births and can cause hypoglycaemia.Endocrine causes of hypoglycaemia.

Endocrine disorders resulting in deficiencies of hormonesantagonistic to insulin are rare but well-recognized causes
of hypoglycaemia. These include hypopituitarism, isolated adrenocorticotrophic hormone (ACT H) deficiency and Addison’s disease.

Drug-induced hypoglycaemia

Many drugs have been reported to produce isolated cases of hypoglycaemia, but usually only when other predisposing factors are present. The following are among the more important:
SULPHONYLUREAS may be used in the treatment of diabetes or may be taken by non-diabetics in suicide attempts.
QUININE may produce severe hypoglycaemia in the course of treatment for faJciparum malaria. SALICYLATES may cause hypoglycaemia following accidental ingestion by children, but this complication is very rare in adults.
PROPRANOLOL has been reported to induce hypoglycaemia in the presence of strenuous exercise or starvation.
PENTAMIDINE may cause hypoglycaemia when used in the treatment of resistant Pneumocystis pneumonia in people with AIDS.

Alcohol-induced hypoglycaemia

Alcohol inhibits gluconeogenesis. Alcohol-induced hypoglycaemia was first described in poorly nourished chronic alcoholics but may also present in binge drinkers and in children who have taken relatively small amounts of alcohol, since they have a diminished hepatic glycogen reserve. The clinical presentation is with coma and hypothermia. Factitious hypoglycaemia This is a relatively common variant of self-induced disease and is much more common than an insulinoma. Hypoglycaemia is produced by surreptitious self-administration of insulin or sulphonylureas. Many patients in this category have been extensively investigated for an insulinoma. Measurement of C-peptide levels during hypoglycaemia should identify patients who are injecting insulin; sulphonylurea abuse can be detected by chromatography of plasma or urine.